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Genetic variation and association analyses of NEDD4 gene in Kazak Chinese patients with hypertension.

ABSTRACT: To analyze the association between the genetic variations of neural precursor cell expressed developmentally down-regulated 4 gene (NEDD4) and hypertension in Kazakh Chinese. The sequences of NEDD4 gene exons were sequenced in 96 Kazakh Chinese with hypertension to identify representative variations. A case-control study was conducted by genotyping the representative variations in 287 Kazakh hypertensives and 411 normotensives. Replication population was 343 Uygur hypertensives and 724 normotensives. All subjects were selected from population-based cross-sectional studies of metabolic disease. Thirteen novel and 15 known single nucleotide polymorphism (SNPs) or mutations, including 6 missense mutations, were identified. Of the four representative SNPs geno-typed, only rs2303580 was association with hypertension in Kazakh (additive P/Pc=0.020/0.160) without Bonferroni's correction. The result was replicated in Uygur (additive/dominant P=0.089/0.028, Pc=0.174/0.056). By adjusting for age and BMI, the observed association would no longer be statistically significant in Kazakh (additive OR (95%CI) 1.035(0.802-1.336), but remained statistically significant in Uygur ( additive/dominant ORs (95%CI) 1.323 (1.069-1.637), 1.521(1.146-2.020)). The rs2303580 genotypes were not association with blood pressure levels in Kazakh. Although by multiple linear regression analysis and by applying Bonferroni's correction, the genotypes were significant association with diastolic blood pressure levels (AA>AG>GG) in Uygur normotensive controls (P/Pc=0.003/0.018), the direction of difference was not in accordance with the association between the qualitative hypertension phenotype and the genotype shown (G risk allele). Our data indicates that the association between the NEDD4 genetic polymorphisms and hypertension phenotype should be replicated in further studies using larger and racially diverse populations.

SUBMITTER: Li N

PROVIDER: S-EPMC3076774 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Genetic variation and association analyses of NEDD4 gene in Kazak Chinese patients with hypertension.

Li Nanfang N Guo Yanying Y Zhou Ling L Wang Hongmei H Yao Xiaoguang X Luo Wenli W Chang Jianhang J

International journal of molecular epidemiology and genetics 20100620 3

To analyze the association between the genetic variations of neural precursor cell expressed developmentally down-regulated 4 gene (NEDD4) and hypertension in Kazakh Chinese. The sequences of NEDD4 gene exons were sequenced in 96 Kazakh Chinese with hypertension to identify representative variations. A case-control study was conducted by genotyping the representative variations in 287 Kazakh hypertensives and 411 normotensives. Replication population was 343 Uygur hypertensives and 724 normotens ...[more]

PMID: 21537394

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Project description:BackgroundSchizophrenia is a complex psychiatric disorder with unknown etiology. A number of recent studies have shown that the polymorphism of the neural precursor cell expressed developmentally down-regulated 4 (NEDD4) gene is associated with a variety of neuropsychiatric disorders, such as schizophrenia, and may also be associated with cognitive dysfunction in these diseases.MethodsA case-control study was carried out, the alleles and genotypes distributions of five loci (rs3088077, rs2303579, rs7162435, rs11550869, rs62043855) of the NEDD4 gene from 296 schizophrenia patients and 320 healthy controls were detected by using Taqman single-nucleotide polymorphism (SNP) genotyping technology. The clinical data of case and control group members were collected by self-made questionnaire and the psychotic symptoms of case group members were assessed by the Positive and Negative Syndrome Scale (PANSS). The Matrics Consensus Cognitive Battery (MCCB) was used to test the cognitive function of case group members.ResultsThe alleles and genotypes frequency of two loci (rs3088077, rs2303579) between case and control group showed significant differences (P < 0.05). There was no significant difference in MCCB scores of patients with different genotypes at rs3088077, rs11550869 and rs7162435 loci in case group. The study of rs2303579 locus showed that, patients' scores with CT genotype were significantly lower than those with CC and TT genotypes (P < 0.05) in the test of Wechsler Memory Scale-Third Edition (WMS-III): Spatial Span, the scores of patients with TT genotype were significantly higher than those with CT genotype (P < 0.05) in the test of Hopkins Verbal Learning Test-Revised (HVLT-R). The study of rs62043855 locus showed that patients with TG genotype had significantly lower scores than those with GG genotype (P < 0.05) in the test of Neuropsychological Assessment Battery (NAB): Mazes.ConclusionsOur study showed that in schizophrenia patients of Chinese Han population, the polymorphisms of rs3088077 and rs2303579 loci were related to the pathogenesis of schizophrenia, while the polymorphisms of rs2303579 and rs62043855 loci were associated with cognitive dysfunction.

Dataset Information

Genetic variation and association analyses of NEDD4 gene in Kazak Chinese patients with hypertension.

Publications

Genetic variation and association analyses of NEDD4 gene in Kazak Chinese patients with hypertension.

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